Objective: To identify determinants of low birth weight (LBW) in Karachi, Pakistan, including environmental exposures and nutritional status of the mother during pregnancy. Design: Cross-sectional study. Participants: Five hundred and forty mother-infant pairs. We interviewed mothers about obstetric history, diet and exposure to Pb. We measured birth weight and blood lead level (BLL). We performed multiple log binomial regression analysis to identify factors related to LBW. Results: Of 540 infants, 100 (18.5%) weighed ≤2.5 kg. Umbilical cord BLL was not significantly associated with LBW. Maternal poor self-rated health (adjusted prevalence ratio (adjPR) = 1.83; 95% CI 1.09, 3.07) and none or one prenatal visit (adjPR = 2.18; 95% CI 1.39, 3.43) were associated with LBW. A statistically significant interaction between mothers' mid upper-arm circumference (MUAC) and dietary vitamin C intake was noted. Compared with mothers with MUAC above the median and dietary vitamin C intake above the 3rd quartile (>208.7 mg/d), infants of mothers with MUAC less than or equal to the median and dietary vitamin C intake >208.7 mg/d (adjPR = 10.80; 95% CI 1.46, 79.76), mothers with MUAC above the median and vitamin C intake >208.7 mg/d (adjPR = 10.67; 95% CI 1.50, 76.02) and mothers with MUAC less than or equal to the median and vitamin C intake >208.7 mg/d (adjPR = 13.19; 95% CI 1.85, 93.79) more likely to give birth to an LBW infant. Conclusions: In Pakistan, poor nutritional status and inadequate prenatal care were major determinants of LBW in this setting. Environmental factors including umbilical cord BLL were not significantly associated with LBW. Copyright © The Authors 2008.